Inhibition of 1 alpha-hydroxy-vitamin D3 stimulated bone resorption in tissue culture by the calcium antagonist verapamil.
The effect of the calcium antagonist verapamil on 1 alpha-hydroxy-vitamin D3 (1 alpha (OH)D3) stimulated bone resorption in tissue culture has been investigated. It was found that verapamil in concentrations above 20 mumol/l reduced 1 alpha (OH)D3-stimulated mineral mobilization, as measured by release of in vivo incorporated 45Ca from mouse calvarial bones. The inhibition of verapamil could be seen already 3 h after exposure to the drug. The increased degradation by 1 alpha (OH)D3 of the organic matrix in the calvaria, as assessed by the release of in vivo 3H-proline labelled collagen, was also reduced by verapamil. The inhibitory effect of the drug on 45Ca release was reversible after withdrawal. 1 alpha (OH)D3 increased the release of stable calcium and beta-glucuronidase, and these effects could be blocked by verapamil. Increasing medium calcium concentration from 1.8 to 5 mmol/l slightly reduced the inhibitory capacity of 50 mumol/l verapamil on 1 alpha (OH)D3-stimulated 45Ca release. These data indicate that stimulation of osteoclasts by hydroxylated metabolites of vitamin D to resorb bone and secrete lysosomal enzyme is dependent on an increased availability of free intracellular calcium.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006887:Hydroxycholecalciferols / Q000037:antagonists & inhibitors*; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D006887:Hydroxycholecalciferols; C026443:26-hydroxycholecalciferol; D014700:Verapamil; D005966:Glucuronidase; D002118:Calcium